Fig. 2: Increase in circulating GP73 elevates fasting blood glucose.
From: GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia
a, Plasma glucose levels at the indicated times after a single dose of i.v. rmGP73 (0.1 mg kg−1) or PBS in mice subjected to a preceding 12 h fast (n = 6). P = 0.0047 for rmGP73 versus PBS (15 min), P = 0.0065 for rmGP73 versus PBS (30 min), P < 0.0001 for rmGP73 versus PBS (60 min), P = 0.0084 for rmGP73 versus PBS (90 min) and P = 0.0018 for rmGP73 versus PBS (120 min) by two-way ANOVA followed by Bonferroni’s post hoc test. b, Plasma insulin levels 15 min after rmGP73 injection (n = 6). P < 0.0001 for rmGP73 versus PBS (15 min) by two-tailed Student’s t-tests. c, Plasma glucose levels 15 min after rmGP73 injection with IgG isotype or anti-GP73 antibody (n = 5). P = 0.0027 for rmGP73 versus PBS (isotype), P = 0.0067 for anti-GP73 versus isotype (rmGP73) by one-way ANOVA followed by Bonferroni’s post hoc test. d, Plasma glucose levels at the indicated times after rmGP73 injection once daily for 3 d (n = 6). P = 0.0016 for first versus PBS, P < 0.0001 for second versus PBS, P = 0.0020 for third versus PBS by two-way ANOVA followed by Bonferroni’s post hoc test. e–h, ITT (e), intravenous glucose tolerance test (IGTT; f), PTT with or without anti-GP73 antibody (g) or alanine tolerance test (ATT; h) in mice 2 h after rmGP73 injection (n = 5 or 6). P = 0.6384 for rmGP73 versus PBS by two-way ANOVA test (e), P < 0.0001 for rmGP73 versus PBS (30 min and 60 min), P = 0.0012 for rmGP73 versus PBS (90 min), P = 0.0176 for rmGP73 versus PBS (120 min) by two-way ANOVA followed by Bonferroni’s post hoc test (f), P < 0.0001 for rmGP73 + anti-GP73 versus rmGP73 + isotype (15 min, 30 min, 60 min, 90 min and 120 min) (g), P = 0.0046 for rmGP73 versus PBS (0 min), P = 0.0126 for rmGP73 versus PBS (15 min), P = 0.0063 for rmGP73 versus PBS (30 min) (h) by two-way ANOVA followed by Bonferroni’s post hoc test. i, Plasma glucose levels 15 min after injection of IgG isotype or anti-GP73 antibody in mice subjected to a preceding 12 h fast (n = 5). P = 0.0036 for anti-GP73 versus isotype by two-tailed Student’s t-tests. j, Immunoblotting (IB) analysis of AKT phosphorylation (AKT-p) in PMHs, HepG2 or L6 cells treated with the indicated concentrations of insulin in the presence or absence of GP73. Animal and cell-based studies were performed independently at least three biological replicates with comparable results. Data are mean ± s.e.m. *P < 0.05,**P < 0.01, ***P < 0.001.
